Most of this effort revolves around a large and complex model of the energy metabolism of the heart, which has been brought to the point of simulating a large amount of data from several sources. Since this model includes submodels of the individual enzymes and of the mitochondria in situ, it is an effective vehicle for studying the properties of these entities in situ. This is expected to be done, by sensitivity analysis, by substitution of alternate enzyme forms for those in the model, by simulation of commonly used in vitro conditions, etc. A counterpart liver model is also expected to be constructed, by substitution of appropriate isozymes, numbers, etc., for their counterparts in the heart model; it will then be used to study selected sets of experimental data. Simulation of procedures in clinical enzymology will be carried out, starting with the serum transaminases, for which we have models with partial results. We expect to continue to make methodological improvements, especially with a view to improving the economics of the simulation process, including usage of less computer memory, better numerical solution methods, and methods of decomposition and sub-modeling.